# NAD+: The Redox Coenzyme Sirtuins, PARPs and CD38 Compete For > NAD+ is the cell's central redox coenzyme and a consumed signaling substrate; tissue NAD+ falls with age. A cited research digest of NAD+, its precursors NMN and NR, and what trials actually measured. A pinned-up digest of the published research on NAD+ and its precursors — what raises blood NAD+, what stays unproven, and where the honest gaps are. Every quantitative claim is tacked to its study. ## The short version NAD+ (a fuel-handling helper molecule every cell uses to turn food into energy) is found in every living cell, and tissue levels of it fall as we age. It is not a drug and not one product — it is sold as a dietary supplement, and most oral capsules are actually a precursor (a building block the body converts into NAD+ — NMN and NR are the common ones), because NAD+ itself is large and poorly absorbed when swallowed. Three families of enzymes spend NAD+ as they work: sirtuins, PARPs, and CD38. This page is a research digest of what studies have measured, not advice and not a recommendation to take anything. ## What NAD+ actually is, and why it matters NAD+ (nicotinamide adenine dinucleotide) is the cell's central redox coenzyme — a coenzyme (a helper molecule an enzyme needs to do its job) — and a consumed signaling substrate at the same time. As a redox carrier (redox is the chemistry that shuttles electrons to release energy), NAD+ shuttles electrons through glycolysis, the TCA cycle and oxidative phosphorylation to make ATP, the cell's energy currency. As a substrate, it is spent by three enzyme families — sirtuins, PARPs and CD38 — that govern DNA repair, gene regulation and inflammation [5]. The single most reproduced observation in this field is simple: tissue NAD+ declines with age across yeast, worms, mice and humans [5]. Part of that decline is driven by CD38 (an NAD-consuming ectoenzyme that rises with age and inflammation); in mice, deleting CD38 protects against the age-related fall in NAD+ [2]. That decline is the rationale behind the entire NAD+ supplement category — and the [reported side effects and tolerability](/faq) of the products built around it are summarized across this board. NAD+ is a single endogenous molecule (CAS 53-84-9, molecular weight 663.43 Da, formula C21H27N7O14P2). It is not a peptide, not a protein, and not a marketed drug. This site reads the literature as a pinned research board: each study, each enzyme, each precursor gets its own card, and the gaps are flagged in plain sight. ## NAD+ as a Dietary Supplement: What the Research Shows An oral NAD supplement is regulated as a dietary supplement, not a drug — NAD+ is not FDA-approved for any disease. The practical catch is bioavailability: NAD+ itself is large and charged, and it is poorly taken up by cells intact, so swallowing "NAD+" capsules is an inefficient way to raise it. That is why the products that have actually been tested in people are usually precursors — NMN, NR, and the vitamin-B3 forms niacin and nicotinamide — which the body converts into NAD+ along the salvage pathway [5]. What the controlled human evidence consistently shows is that oral precursors raise whole-blood NAD+ in a dose-dependent way. In healthy overweight adults, [nicotinamide riboside (NR)](/nicotinamide-riboside) at 100, 300 and 1000 mg/day for 8 weeks raised whole-blood NAD+ by 22%, 51% and 142% respectively, with no flushing and no significant adverse-event difference from placebo [4]. Raising the blood number is well established. Whether that translates to hard clinical outcomes in people is the open question of the field [13]. ## NMN (Nicotinamide Mononucleotide): The Other Major Precursor NMN (nicotinamide mononucleotide) sits one biochemical step from NAD+ and is the precursor most often paired against NR. In a randomized, multicenter, double-blind trial in healthy middle-aged adults, oral NMN at 300, 600 or 900 mg/day for 60 days raised blood NAD+ at days 30 and 60 across every dose group versus placebo (p ≤ 0.001), with 600 mg/day identified as the optimal dose and no safety issues at any dose [3]. A separate trial in prediabetic, postmenopausal women found that 250 mg/day for 10 weeks improved muscle insulin sensitivity without changing body composition or HbA1c [1]. NMN carries one wrinkle the other precursors do not: its regulatory status is contested. The FDA has taken the position that NMN is excluded from the dietary-supplement definition because it was authorized for investigation as a drug. That is a live marketplace dispute, not a settled ban — and it is reported here as exactly that. NAD+ versus its precursors is unpacked on the [nicotinamide riboside (NR)](/nicotinamide-riboside) page. ## Three enzymes, one shrinking pool The lens this board is organized around is competition. Sirtuins (a family of cellular-maintenance enzymes that can't work without NAD+), PARP1 (a DNA-repair enzyme that consumes large amounts of NAD+ when DNA is damaged), and CD38 all draw on the same NAD+ pool, and as that pool shrinks with age the demand does not [5]. Sirtuins spend NAD+ to deacylate target proteins; the mitochondrial sirtuin SIRT3 regulates mitochondrial biogenesis through the AMPK–PGC-1α axis [9]. CD38 is the standout driver of the age-related decline: a specific CD38 inhibitor reversed age-related metabolic dysfunction in aged mice by restoring tissue NAD+ [8]. This is why "boost NAD+" is the marketing pitch, and why the biology is more interesting than the pitch. The full account — including how the circadian clock paces NAD+ synthesis — lives on the [sirtuins and the NAD+ axis](/sirtuins-and-nad) page, [the human clinical trials](/research) are summarized in full on the research page, and the [doses used in the research](/dosage) are catalogued separately. --- A pinned-up research board on NAD+ — the redox coenzyme and its precursors NMN and NR tacked to their studies, the dose-dependent blood-NAD+ data marked confirmed and the unproven human endpoints flagged in red, with no clinic behind the board and nothing here infused, dispensed, or sold.